Systematic Characterization of Autophagy in Gestational Diabetes Mellitus

Ji, Lulu; Chen, Zhiguo; Xu, Yating; Xiong, Guoping; Liu, Rui; Wu, Chao; Hu, Hanyang; Wang, Lin

doi:10.1210/en.2016-1922

Cited by 45 publications

(26 citation statements)

References 52 publications

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“…Because of the sensitivity of NSCs to autophagy, more study methods need to be used to estimate the relationship between stress and autophagy. Studies have also reported that HG contributes to autophagy in retinal cells and placenta . However, HG has also been shown to impair autophagy in endothelial progenitor cells and umbilical vein endothelial cells .…”

Section: Discussionmentioning

confidence: 98%

Melatonin Enhances Proliferation and Modulates Differentiation of Neural Stem Cells Via Autophagy in Hyperglycemia

Zhang

Liu

et al. 2019

Stem Cells

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Dysfunction of neural stem cells (NSCs) has been linked to fetal neuropathy, one of the most devastating complications of gestational diabetes. Several studies have demonstrated that melatonin (Mel) exerted neuroprotective actions in various stresses. However, the role of autophagy and the involvement of Mel in NSCs in hyperglycemia (HG) have not yet been fully established. Here, we found that HG increased autophagy and autophagic flux of NSCs as evidenced by increasing LC3B II/I ratio, Beclin-1 expression, and autophagosomes. Moreover, Mel enhanced NSCs proliferation and self-renewal in HG with decreasing autophagy and activated mTOR signaling. Consistently, inhibition of autophagy by 3-Methyladenine (3-Ma) could assist Mel effects above, and induction of autophagy by Rapamycin (Rapa) could diminish Mel effects. Remarkably, HG induced premature differentiation of NSCs into neurons (Map2 positive cells) and astrocytes (GFAP positive cells). Furthermore, Mel diminished HG-induced premature differentiation and assisted NSCs in HG differentiation as that in normal condition. Coincidentally, inhibiting of NSCs autophagy by 3-Ma assisted Mel to modulate differentiation. However, increasing NSCs autophagy by Rapa disturbed the Mel effects and retarded NSCs differentiation. These findings suggested that Mel supplementation could contribute to mimicking normal NSCs proliferation and differentiation in fetal central nervous system by inhibiting autophagy in the context of gestational diabetes. STEM CELLS 2019;37:504-515 SIGNIFICANCE STATEMENTNeural stem cells play important roles in fetal neurodevelopment. The incidences of gestational diabetes are rising in the world and prevention of fetal neuropathy in gestational diabetes mellitus (GDM) needs to be deeply explored. In addition, autophagy of NSCs in HG is still unclear. Here, it is reported that HG inhibits proliferation and induces premature differentiation of NSCs by promoting autophagy and autophagic flux. The naturally occurring hormone melatonin (Mel) antagonized HG-mediated effects and maintained normal proliferation and differentiation in NSCs by modulating autophagy, which protected NSCs mainly by downregulating Beclin-1 and up modulating mTORC1 signaling. This work indicates that Mel could be used as a potential drug to aid in fetal central nervous system (CNS) development in GDM patients.

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Section: Discussionmentioning

confidence: 98%

Melatonin Enhances Proliferation and Modulates Differentiation of Neural Stem Cells Via Autophagy in Hyperglycemia

Zhang

Liu

et al. 2019

Stem Cells

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“…Autophagy, an evolutionarily conserved catabolic process, is important in maintenance of cellular homeostasis. 36 However, autophagy dysfunction is related to many diseases, [37][38][39] including cancer. 40 High levels of autophagy have been observed during cell death, and it has been shown to be induced by various chemotherapeutic agents.…”

Section: Food and Function Papermentioning

confidence: 99%

Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models

et al. 2018

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“…However, we have previously shown that overexpression of FKBPL inhibited migration and invasion of cancer cells. 21,59 Considering that hyperglycaemia has the potential to decrease trophoblast invasion, 60 FKBPL expression was found to be reduced in high glucose conditions, but only in the presence of low oxygen levels, which suggests that FKBPL may be important in determining primary trophoblast invasion during the first trimester of pregnancy in women with diabetes.…”

Section: Discussionmentioning

confidence: 99%

FKBPL and SIRT-1, key angiogenesis proteins, are downregulated by diabetes in pregnancy

Alqudah

Eastwood

Jerotić

et al. 2020

Preprint

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Context Diabetes in pregnancy is associated with numerous complications, however the mechanisms are still poorly understood. Objective To investigate the role of new angiogenesis markers, FKBPL and SIRT-1, in pre-gestational (type 1 diabetes, T1D) and gestational diabetes (GDM). Design and intervention Placental FKBPL, SIRT-1, PlGF and VEGF-R1 protein expression was determined from pregnant women with GDM or T1D, and in first trimester trophoblast cells exposed to high glucose and varying oxygen concentrations. Endothelial cell function was assessed in high glucose conditions and FKBPL overexpression. Settings and Participants Human placental samples from pregnant women with GDM (n=6) or T1D (n=8) were collected to assess FKBPL and SIRT-1 protein expression compared to non-diabetic controls. Main outcome measures To determine the role of placental FKBPL and/or SIRT-1 in diabetic pregnancies, in first trimester trophoblasts and endothelial cell function in high-glucose environment. Results Placental FKBPL protein expression was downregulated in T1D (FKBPL; p<0.05) whereas PlGF/VEGF-R1 were upregulated (p<0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 (p<0.001) was significantly downregulated even when adjusted for gestational age (r=-0.92, p=0.001). FKBPL and SIRT-1 were also downregulated in ACH-3P cells in high glucose conditions and 6.5%/2.5% oxygen concentrations (p<0.05). FKBPL overexpression in HUVECs reduced tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05). Conclusions FKBPL and/or SIRT-1 downregulation in response to diabetes may have a role in the development of vascular dysfunction in pregnancy, and associated complications such as preeclampsia.

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Systematic Characterization of Autophagy in Gestational Diabetes Mellitus

Cited by 45 publications

References 52 publications

Melatonin Enhances Proliferation and Modulates Differentiation of Neural Stem Cells Via Autophagy in Hyperglycemia

Melatonin Enhances Proliferation and Modulates Differentiation of Neural Stem Cells Via Autophagy in Hyperglycemia

Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models

FKBPL and SIRT-1, key angiogenesis proteins, are downregulated by diabetes in pregnancy

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